Yuval Dor was born in Jerusalem and earned his PhD in molecular vascular biology at the Hebrew University in 2001. He then moved to Harvard University and trained with Doug Melton until 2004, when he return to Israel to establish his independent group at the Hebrew University.
His lab is studying tissue dynamics during postnatal life: the molecular mechanisms by which cell regenerate and die. Much of his work focuses on pancreatic beta cell biology in the context of diabetes, as well as on pancreatic cancer. In recent years he has developed a novel method to study cell death in humans, using methylation signatures of DNA circulating in blood which is released by dying cells. Using this method he was able to monitor in real time cell death in multiple pathologies, opening the way to both early diagnosis and monitoring of disease progression and response to therapy. A current focus, in collaboration with neurologists Vaknin (Hadassah) and Ruprecht (Charite), is the study of brain cell death in the context of multiple sclerosis.
Non-invasive detection of tissue damage in multiple sclerosis using cell-free DNA
Axonal loss is well known to correlates with the rate of clinical progression in patients with MS. There are currently no reliable biomarkers to directly measure ongoing neurodegeneration in the brain, a major barrier for progress in research and therapy for demyelinating diseases. We propose to develop a novel type of body fluid biomarker for the detection of brain cell death in MS, thus allowing us to report on real-time brain damage in patients.
The circulation contains fragments of genomic DNA released from dying cells. In extensive studies over the last 4 years, we have developed an approach to identify the origins of cfDNA based on tissue-specific methylation signatures, allowing us to distinguish neurons and oligodendrocytes from all other cell types, Furthermore, we can quantify fragments of cfDNA carrying these signatures; this will directly reflect the rate of brain cell death at the time of sampling.
In this study, we aim to compare cross-sectionally levels of oligodendrocyte and neuronal cfDNA in plasma of patients with different MS subtypes and healthy controls and to analyse the association of oligodendrocyte and neuronal cfDNA with clinical and radiological disease markers for MS. Furthermore, we will analyse the predictive value of these signatures in plasma for disability progression and for conversion to clinically or radiologically definite MS
Utimately, the development of reliable biomarkers and signatures of disease progression will allow for improved monitoring disease activity, response to therapy, relapse and progression.
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